Maarten Cozijnsen

97 Chapter 5 Adalimumab therapy in children with infliximab-refractory CD Introduction Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) that presents before the age of 20 in 25-30% of its patients.(1) In the Netherlands, the reported incidence of CD in children and adolescents under the age of 18 is 2.1 per 100,000.(2) CD manifests more severely in childhood and adolescence than in adulthood, with growth retardation and delayed puberty, worse malnutrition and a higher risk of complications such as strictures, abscesses or fistulas.(1, 3) For pediatric CD patients, first-line treatment consists of exclusive enteral nutrition or corticosteroids to induce remission and thiopurines or methotrexate to maintain it. If this first-line of treatment fails, anti-tumor necrosis factor (TNF) antibody therapy is often indicated.(4) The first anti-TNF antibody that was studied in and registered for CD patients was infliximab, a chimeric (mouse/human) monoclonal antibody. Infliximab both induces and maintains remission in CD patients.(5, 6) Unfortunately, one-third of these patients withdraw from infliximab therapy within three years, and half withdraw within five years.(6, 7) Some withdraw because they never respond to the drug, but most because they lose response. One known reason for loss of response to infliximab is development of antibodies- to-infliximab (ATI) that neutralize the drug.(8, 9) To reduce such an antibody reaction, adalimumab, a fully humanized anti-TNF monoclonal antibody, was developed and tested for CD treatment.(10, 11) Its efficacy and safety in pediatric patients has been studied in one large prospective study(12) and two retrospective studies(13, 14). The positive results from the prospective study have led to registration of adalimumab for pediatric usage. In this Dutch nationwide study, we aimed to evaluate the real-world efficacy of adalimumab in pediatric CD patients who previously failed treatment with infliximab. We included both patients who had no response to infliximab as well as those who lost response, and compared adalimumab efficacy between these two groups.